Structural valvular deterioration of xenogenic heart valve replacements is thought to be due to a chronic immune response. We sought to engineer porcine extracellular matrix that elicits minimal inflammatory immune response. Whole blood, bone marrow and pericardium were collected from patients undergoing elective cardiac surgery. Porcine extracellular matrix was decellularized, reseeded with homologous mesenchymal stem cells and exposed to whole blood. DAPI stain confirmed the absence of cells after decellularization, and presence of mesenchymal stem cells after recellularization. There was a significant reduction in IL-1β and TNF-α production in the recellularized matrix. Recellularization of porcine matrix is successful at attenuating the xenogenic immune response and may provide a suitable scaffold to address the current limitations of prosthetic heart valve replacements.